A comprehensive analysis integrating phenotypic assessment uncovering thornless cultivar lineages in Aralia elata.

Aralia elata is an Araliaceae woody plant species found in Northeastern Asia. To understand how genetic pools are distributed for A.elata clones, we were to analyze the population structure of A.elata cultivars and identify how these are correlated with thorn-related phenotype which determines the utility of A.elata. We found that the de novo assembled genome of 'Yeongchun' shared major genomic compartments with the public A.elata genome assembled from the wild-type from China. To identify the population structure of the 32 Korean and Japanese cultivars, we identified 44 SSR markers and revealed three main sub-clusters using ΔK analysis with one isolated cultivar. Machine-learning based clustering with thorn-related phenotype correlated moderately with population structure based on SSR analysis suggested multi-layered genetic regulation of thorn-related phenotypes. Thus, we revealed genetic lineage of A.elata and uncovered isolated cultivar which can provide new genetic material for further breeding.

Zinc deficiency triggers hearing loss by reducing ribbon synapses of inner hair cells in CBA/N mice.

Zinc plays a vital role in our metabolism, encompassing antioxidant regulation, immune response, and auditory function. Several studies have reported that zinc levels correlate with hearing loss. We have previously demonstrated that the auditory brainstem response (ABR) threshold increased in mice fed a zinc-deficient diet. However, the effects of zinc deficiency on hearing were not fully elucidated. The present study investigated whether zinc deficiency affects hearing in association with neuronal components or cochlear structures. CBA/N mice were fed a normal or zinc-deficient diet for 8 weeks and assessed for ABR and distortion product otoacoustic emissions (DPOAE). The cochlear sections were stained with hematoxylin and eosin solution. Also, we observed the expression of synaptic ribbons, neurofilaments, and alpha-synuclein (α-Syn). The 8-week zinc-deficient diet mice had an elevated ABR threshold but no changed DPOAE threshold or cochlear structures. A reduced number of synaptic ribbons of inner hair cells (IHCs) and impaired efferent nerve fibers were observed in the zinc-deficient diet mice. The number of outer hair cells (OHCs) and expression of α-Syn remained unchanged. Our results suggest that zinc-mediated hearing loss is associated with the loss of neuronal components of IHCs.

Skin electronics from scalable fabrication of an intrinsically stretchable transistor array.

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.

Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

PURPOSE: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. METHODS: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. RESULTS: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. CONCLUSION: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Aspirin use and risk of hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis.

BACKGROUND AND AIMS: Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver-associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis. APPROACH AND RESULTS: We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver-associated mortality, and major bleeding were estimated in a propensity-score-matched cohort (19,003 pairs), accounting for competing risks. With a median follow-up of 6.7 years, 10-year cumulative incidence of HCC was 9.5% in the aspirin-treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78-0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85-1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (pinteraction , n = 0.04). Aspirin use was also associated with lower liver-associated mortality (aSHR, 0.80; 95% CI, 0.71-0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99-1.21). CONCLUSIONS: Aspirin use was associated with reduced risks of HCC and liver-associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.

Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke.

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke.

Status of the Newborn Hearing Screening in the 4-Months Age National Infant Health Checkup in Korea: A Nationwide Population-Based Study.

BACKGROUND: The aims of this study are to review data on 4-months age National Health Screening Program for Infants and Children (NHSPIC) using a National Health Insurance Service (NHIS) database, and to analyze the newborn hearing screening (NHS) results and related characteristics of the 4-months NHSPIC for 7 years in South Korea. METHODS: We analyzed a NHIS database of infants who had participated in the 4-month age NHSPIC from 2010 to 2016. According to the results of hearing questionnaires and physical examination, we analyzed the outcomes of NHS and related infantile and socioeconomic factors. RESULTS: Among 3,128,924 of total eligible infants in Korea between the year 2010 and 2016, 69.2% (2,164,621 infants) conducted 4-months age NHSPIC, and 94.4% (2,042,577 infants) of which performed hearing questionnaires regarding NHS. Among the total hearing examinees, premature infants accounted for 3.6%, infants who were hospitalized in the neonatal intensive care unit (NICU) for more than 5 days accounted for 5.6%, and infants with head and neck abnormalities were 0.6%. The NHS performing rate was 79.1% for total hearing examinees in 2010, but gradually increased to 88.9% in 2016. The NHS performing rate in 2016 was 93.4% for premature infants, 91.7% for NICU hospitalized babies. The mean referral rate was 0.6% for total hearing examinees, 1.4% for premature infants, and 2.3% for NICU hospitalized babies. When we analyzed the NHS performing rate and the referral rate according to the household income level, the NHS performing rate of infants in Medical Aid programs was the lowest as 65.6%, and the NHS performing rates in other five levels of NHIS was higher ranging between 85.1% to 86.0%. The referral rate of infants in the Medical Aid program (3.8%) was significantly higher than those of infants in other classes (1.10-1.25%). CONCLUSION: The estimated overall NHS performing rate in Korea gradually increased and was 88.9% in 2016. The overall referral rate was low as 0.6%, and it was significantly different depending on the infant's health condition and household income levels. We assume that our finding would help to establish policies managing hearing impaired children, and to develop the customized hearing care service programs considering the household economic levels.

Keratinized tissue augmentation using collagen-based soft tissue substitute with/without epidermal growth factor on buccally positioned implants: a pilot preclinical study.

OBJECTIVES: To investigate the effect of epithelial growth factor (EGF) with collagen matrix (CM) on the gain of KT for buccally positioned implants in dogs. MATERIALS AND METHODS: In five dogs, four implants were placed buccally with the whole part of KT excision on the buccal side (two implants per each hemi-mandible). After one month, KT augmentation was performed: 1) free gingival grafts (FGG), 2) collagen matrix (CM) only, 3) CM soaked with 1 µg/g of EGF, and 4) CM soaked with 10 µg/g of EGF (n = 5 in each group). The experimental animals were sacrificed three months post-KT augmentation. Clinical, histologic, and histomorphometric analyses were performed. RESULTS: The clinical KT zone was the highest in group FGG (5.16 ± 1.63 mm). Histologically, all groups presented buccal bony dehiscence. Regarding newly formed KT, no specific difference was found among the groups, but robust rete pegs formation in some specimens in group FGG. Histomorphometric KT height (4.66 ± 1.81 mm) and length (5.56 ± 2.25 mm) were the highest in group FGG, whereas similar increases were noted in the rest. The buccal soft tissue thickness at the coronal part of the implant did not exceed 2 mm in all groups. CONCLUSION: All groups presented increased KT zone, but FGG treatment was more favored. The addition of EGF to CM appeared not to enhance KT formation. CLINICAL RELEVANCE: FGG treatment was more favorable to re-establish the KT zone than other treatment modalities.

Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells.

In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.

Association between Pneumonia Development and Virulence Gene Expression in Carbapenem-Resistant Acinetobacter baumannii Isolated from Clinical Specimens.

We investigated the virulence gene expression of carbapenem-resistant Acinetobacter baumanii (CRAB) isolated from the respiratory samples of patients with CRAB pneumonia and those with CRAB colonization to identify the virulence genes contributing to CRAB pneumonia's development and mortality. Patients with CRAB identified from respiratory specimens were screened at a tertiary university hospital between January 2018 and January 2019. Patients were classified into CRAB pneumonia or CRAB colonization groups according to predefined clinical criteria. A. baumannii isolated from respiratory specimens was examined for the expression levels of ompA, uspA, hfq, hisF, feoA, and bfnL by quantitative reverse-transcription polymerase chain reaction. Among 156 patients with CRAB from respiratory specimens, 17 and 24 met the criteria for inclusion in the pneumonia and colonization groups, respectively. The expression level of ompA was significantly higher in the pneumonia group than in the colonization group (1.45 vs. 0.63, P=0.03). The expression levels of ompA (1.97 vs. 0.86, P=0.02), hisF (1.06 vs. 0.10, P < 0.01), uspA (1.62 vs. 1.01, P < 0.01), and bfnL (3.14 vs. 2.14, P=0.03) were significantly higher in patients with 30-day mortality than in the surviving patients. Elevated expression of hisF (adjusted odds ratio = 5.93, P=0.03) and uspA (adjusted odds ratio = 7.36, P=0.02) were associated with 30-day mortality after adjusting for age and the Charlson score. uspA and hisF may serve as putative targets for novel therapeutic strategies.

Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial.

BACKGROUND: Mesenchymal stem cells (MSCs) secrete trophic factors and extracellular vesicles (EVs). However, the level and role of EVs after MSC therapy in patients with stroke are unknown. We investigated whether circulating EVs and trophic factors are increased after MSCs and are related to the therapeutic benefits in the STARTING-2 trial (Stem Cell Application Researches and Trials in Neurology-2) participants. METHODS: In this prospective randomized controlled trial, patients with chronic major stroke were assigned, in a 2:1 ratio, to receive autologous MSC intravenous injection (MSC group, n=39) or standard treatment (control group, n=15) and followed for 3 months. Detailed clinical assessment and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging were evaluated. Serial samples were collected, before/after MSCs therapy. The primary outcome measure was circulating factors that are associated with the clinical improvement in the Fugl-Meyer Assessment (secondary end point of the trial) and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging. Additional outcome measures were microRNAs and trophic factors enriched in the plasma EVs, obtained using quantitative polymerase chain reaction and ELISA, respectively. RESULTS: Circulating EV levels were increased ≈5-fold (mean±SD, from 2.7×109±2.2×109 to 1.3×1010±1.7×1010 EVs/mL) within 24 hours after injection of MSCs (P=0.001). After adjustment of age, sex, baseline stroke severity, and the time interval from stroke onset to treatment, only the EV number was independently associated with improvement in motor function (odds ratio, 5.718 for EV numberLog [95% CI, 1.144-28.589]; P=0.034). Diffusion tensor image and resting-state functional magnetic resonance imaging showed that integrity of the ipsilesional corticospinal tract and intrahemispheric motor network were significantly correlated with circulating EV levels, respectively (P<0.05). MicroRNAs related to neurogenesis/neuroplasticity (eg, microRNA-18a-5p) were significantly increased in circulating EVs after MSC therapy (P=0.0479). In contrast, trophic factor levels were not changed after MSC therapy. CONCLUSIONS: This trial is the first to show that treatment of ischemic stroke patients with MSCs significantly increases circulating EVs, which were significantly correlated with improvement in motor function and magnetic resonance imaging indices of plasticity. REGISTRATION: URL: https://www. CLINICAL TRIALS: gov; Unique identifier: NCT01716481.

Efficacy of Intravenous Mesenchymal Stem Cells for Motor Recovery After Ischemic Stroke: A Neuroimaging Study.

BACKGROUND AND PURPOSE: Stem cell-based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell-based therapy in patients with ischemic stroke. METHODS: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. RESULTS: For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. CONCLUSIONS: Stem cell-based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01716481.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

Effects of Dose Titration on Dipyridamole-Induced Headache: A Randomized, Double-Blind Clinical Trial.

PURPOSE: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. RESULTS: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different. CONCLUSION: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache.

Intrinsically stretchable and healable semiconducting polymer for organic transistors.

Thin-film field-effect transistors are essential elements of stretchable electronic devices for wearable electronics. All of the materials and components of such transistors need to be stretchable and mechanically robust. Although there has been recent progress towards stretchable conductors, the realization of stretchable semiconductors has focused mainly on strain-accommodating engineering of materials, or blending of nanofibres or nanowires into elastomers. An alternative approach relies on using semiconductors that are intrinsically stretchable, so that they can be fabricated using standard processing methods. Molecular stretchability can be enhanced when conjugated polymers, containing modified side-chains and segmented backbones, are infused with more flexible molecular building blocks. Here we present a design concept for stretchable semiconducting polymers, which involves introducing chemical moieties to promote dynamic non-covalent crosslinking of the conjugated polymers. These non-covalent crosslinking moieties are able to undergo an energy dissipation mechanism through breakage of bonds when strain is applied, while retaining high charge transport abilities. As a result, our polymer is able to recover its high field-effect mobility performance (more than 1 square centimetre per volt per second) even after a hundred cycles at 100 per cent applied strain. Organic thin-film field-effect transistors fabricated from these materials exhibited mobility as high as 1.3 square centimetres per volt per second and a high on/off current ratio exceeding a million. The field-effect mobility remained as high as 1.12 square centimetres per volt per second at 100 per cent strain along the direction perpendicular to the strain. The field-effect mobility of damaged devices can be almost fully recovered after a solvent and thermal healing treatment. Finally, we successfully fabricated a skin-inspired stretchable organic transistor operating under deformations that might be expected in a wearable device.

Beneficial effects of gamma-irradiation of quinoa seeds on germination and growth.

Quinoa is one of the crops well-adapted to high altitude regions that can grow relatively well under drought, humid, and high UV radiation conditions. This study was performed to investigate the effects of gamma-radiation on quinoa. Seeds were treated with various doses of 50 Gy, 100 Gy, 200 Gy, 300 Gy, 400 Gy, 600 Gy, 800 Gy, and 1000 Gy. We investigated germination, as well as plant height, chlorophyll content, and normalized difference vegetation index (NDVI) at 0, 30, 44, 58, and 88 days after transplanting (DAT) and panicle weight at 88 DAT. The plants grown from the seeds treated at radiation doses greater than 200 Gy showed reduced values in most growth and physiological characteristics. The germination rate and germination speed were higher in the 50 Gy-treated seeds than in 0 Gy-treated (control) seeds. Plant height and panicle weight were highest in the plants from 50 Gy-treated seeds. Chlorophyll content was higher in all treated samples than in the controls. NDVI value showed the highest value in 0 Gy controls and plants treated with 50 Gy. The antioxidant activity was also higher in the plants from the seeds treated with 50 Gy and 100 Gy, showing a steady increase as the radiation dose increased even at 200 Gy. The plants from seeds treated with 0 Gy showed higher expression of proteins related to photorespiration and tubulin chains. The plants from seeds treated with 50 Gy induced more stress-responsive proteins.

Effectiveness of hydraulic pressure-assisted sinus augmentation in a rabbit sinus model: a preclinical study.

OBJECTIVES: To investigate the effectiveness of hydraulic pressure-assisted sinus augmentation (SA) in a rabbit sinus model in terms of radiographical and histological healing. MATERIALS AND METHODS: Bilateral SA was performed in 12 rabbits. Each sinus was randomly assigned to either a hydraulic pressure-assisted SA (test) or a conventional SA (control) group. Healing periods of 2 and 4 weeks were applied (n = 6 for each week). Healing pattern including newly formed bone (NB) and residual bone substitute material (RM) was analyzed with microcomputed tomographically, histologically, and histomorphometrically. RESULTS: No sinus membrane perforation was detected in either group. In the microcomputed tomographic analysis, the test group exhibited higher apico-coronal spread of RM compared to the control group (p < 0.05). Particularly, the test group exhibited several masses of NB out of the cluster of RM. Histologically, the test group showed an elongated shape of the augmented space, whereas the control group generally presented a dome shape. Histomorphometrically, the total augmented area and the area of NB (1.32 ± 0.56 vs. 0.84 ± 0.40 mm2 at 2 weeks, 2.24 ± 1.09 vs. 2.22 ± 0.85 mm2 at 4 weeks) were not significantly different between the test and the control groups at both healing periods (p > 0.05). CONCLUSION: Hydraulic pressure-assisted SA led to new bone formation in the distant areas from the bony access hole, but similar histological healing pattern to conventional SA. CLINICAL RELEVANCE: Hydraulic pressure-assisted SA is a promising option for treating pneumatized posterior maxilla.